AN ULTRASTRUCTURAL EVALUATION OF ACUTE 1-NITRONAPHTHALENE INDUCED HEPATIC AND PULMONARY TOXICITY IN THE RAT

1-Nitronaphthalene is a mutagenic particulate of diesel exhaust which causes acute liver and lung toxicity in rodents. The studies presented here describe morphological changes in the lung and liver at several time intervals following a single injection of 1-nitronaphthalene (100 mg/kg, i.p.) in male Sprague-Dawley rats using transmission and scann ing electron microscopy. Although both the lungs and liver are injured by 1-nitronaphthalene, the lungs appear to be the primary target orga n. Within 4 h of treatment, all 1-nitronaphthalene treated animals exh ibited respiratory distress characterized by labored breathing, severe gasping and chromodacryorrhea. The primary ultrastructural alteration were hydropic changes in the non-ciliated bronchiolar (Clara) cells o f the distal-most bronchioles of the lung. These were apparent as earl y as 1 h after 1-nitronaphthalene injection, while adjacent ciliated c ells showed no alterations. Over a 24 h period, the bronchioles showed progressive ultrastructural changes leading to necrosis and exfoliati on of both ciliated and Clara cells. Interstitial pneumonitis and edem a were observed in all animals treated with 1-nitronaphthalene, and wa s usually associated with bronchioles containing necrotic epithelium. In the liver, ultrastructural changes were observed in the centrilobul ar hepatocytes at 8 h and consisted of cytomegaly, loss of continuous inner membrane and reduced matrix density of the mitochondria. At 48 h , cellular damage to centrilobular hepatocytes was severe and nearly a ll mitochondria were damaged. Elevated levels of alanine aminotransfer ase, aspartate aminotransferase and bilirubin were detected in the ser um of animals treated with 1-nitronaphthalene at 8-48 h. In conclusion , 1-nitronaphthalene is a pulmonary toxicant with a unique progression of injury, which primarily damages Clara cells followed by ciliated c ells. This disparity is likely due to a difference in the bioactivatio n of 1-nitronaphthalene. Furthermore, this systemic toxicant also has injurious effects on the centrilobular region of the liver which prece des lung injury. Copyright (C) 1997 Elsevier Science Ireland Ltd.